Immune Checkpoint Therapy With Nivolumab Esophageal Squamous Cell Carcinoma

NCT03278626 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-00971
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

In this multi-institution phase I/II trial, the investigators have chosen paclitaxel and carboplatin using a schedule and doses identical to those used in the CROSS trial. Following a run-in with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care established by the CROSS trial: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation will be administered with chemotherapy at 1.8 Gy/fraction × 28 fractions to a total dose of 50.4 Gy, the standard radiation dose administered in the United States for trimodality therapy that includes concurrent therapy with carboplatin and paclitaxel. A decrease in dose to 41.4 Gy per the protocol established by van Hagen, et al. will be permitted before discontinuing therapy due to unacceptable toxicity. While the CROSS study administered only 5 weekly doses of chemotherapy during the 5 weeks of radiation, the higher dose of 50.4 Gy (1.8 Gy/fraction ×28 fractions over 5½ weeks) utilized in this study permits for a sixth dose during the additional week of radiation.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Locally Advanced Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Unacceptable Toxicity (UT) Events

  UT is defined as: 1. Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy) 2. any toxicity that results in a \> 2-week delay in chemoradiation

  92 days (up to 28 days after Day 64)

• Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)

  Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue

  5-8 Weeks post radiation treatment (7-8 months after treatment start)

Study Arms (1)

Nivolimumab+Carboplatin/paclitaxel+Radiation

OTHER

240 mg IVPB every 2 weeks for 2 doses, nivolumab at 240 mg every 2 weeks will be added to paclitaxel and carboplatin, which will be dosed according to the standard of care: paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks and radiation

Drug: Nivolimumab+Carboplatin/paclitaxel+Radiation

Interventions

Nivolimumab+Carboplatin/paclitaxel+Radiation DRUG

In the phase I portion of the study, up to six patients will be treated (radiation will be 50.4 Gy (1.8 Gy/fraction × 28 fractions)) and then observed for 28 days (following last day of treatment (Day 64)).

Also known as: Opdivo, Paraplatin, Taxol

Nivolimumab+Carboplatin/paclitaxel+Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, treatment-naive esophageal squamous cell carcinoma
• Previously obtained archival tumor tissue, or tissue obtained by endoscopically guided core biopsy at screening
• TanyN1-3 or T3-4 N0as determined by EUS and PET/CT. All palpable or CT/PET visible lymph nodes outside the usual surgical field must be biopsy-proven negative for cancer.
• All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if technically feasible. Endoscopy reports or subsequent GI clinic note should clearly state both the T and N stage.
• All patients must have initial PET/CT scans to document no evidence of metastatic or unresectable squamous cell cancer
• All patients with tumors involving the thoracic esophagus must undergo bronchoscopy to document the absence of a fistula No known contraindication to the use of taxanes or platinum compounds.
• No history of severe hypersensitivity reaction to Cremophor® EL.
• Patients who are ≥ 18 years old are eligible for this study. Neither specific gender distribution, nor specific racial or ethnic origins are necessary for enrollment in this study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• A patient must be capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject's behalf
• Deemed a suitable candidate for esophagectomy by the treating surgeon as documented in a pre-operative assessment visit per standard practice at each participating institution.
• Deemed a suitable candidate for radiation therapy by the treating radiation oncologist as documented in a standard pretreatment visit per standard practice at each participating institution.
• Patient must be non-pregnant and non-nursing. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to C1D1.
• Screening Laboratory Values must meet the following criteria and should be obtained within 14 days prior to C1D1 (see Table 1 below)
• Patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement; Patients with HBV core positive, must have negative viral load measurements

You may not qualify if:

• T1-2 N0 as determined by EUS and PET/CT.
• Pregnant or lactating women
• Active or prior documented autoimmune or inflammatory disorders including but not limited to inflammatory bowel disease; systemic lupus erythematosus; type I diabetes mellitus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
• The use of immunosuppressive medication within 28 days prior to the first dose of nivolumab. The following are exceptions to this criterion:
• Intranasal, topical, inhaled corticosteroids or local steroid injections (e.g. intra-articular injection)
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication
• Positive test for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Active Hepatitis B or Hepatitis C (defined as positive-HBV surface antigen or detectable HCV-antibody) indicating acute or chronic infection. Patients with a positive Hepatitis B core antibody (HBVcAb) must have negative viral load measurement.
• Prior treatment with any immunotherapy
• Any other factors, including psychiatric or social, that in the opinion of the treating physician makes the patient an inappropriate candidate for a study.
• Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for \[lowest minimum is 4 weeks or more\] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no ESCC Nivolumab requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (5)

University of Califonia, San Diego

La Jolla, California, 92093, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Nivolumab; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Jennifer Wu, MD
• Organization: NYU Langone Health - Perlmutter Cancer Center

Jennifer.Wu@nyulangone.org

212-263-3809

Study Officials

• Jennifer Wu, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 11, 2017
• Study Start: June 27, 2017
• Primary Completion: November 7, 2019
• Study Completion: May 31, 2021
• Last Updated: March 28, 2022
• Results First Posted: March 28, 2022

Record last verified: 2022-03

Locations

US (5)